Human Cytomegalovirus (CMV) is a herpesviruses which frequently causes life-threatening infections in AIDS patients and other immunocompromised individuals. Preliminary studies suggest that CMV may augment human immunodeficiency virus (HIV) gene expression and replication and thus contribute to the development of AIDS in an HIV-infected individual. The converse interaction, activation of CMV gene expression by HIV, may be pertinent to the occurrence of unusual and severe CMV infections in AIDS patients. This proposal is designed to elucidate the direct molecular interactions of these two viruses. HIV regulatory sequences which respond to CMV infection will be identified and precisely mapped using transient assays. The level(s) of gene expression affected by such signals will be characterized by a comprehensive analysis of alterations in transcription, processing, stability, nuclear/cytoplasmic transport and translation conferred on a transcript by HIV cis-acting signals. The CMV gene products responsible for altering HIV gene expression will be identified and characterized. The converse interaction, the effects of HIV on CMV-regulated gene expression, will also be investigated. Cis-acting signals that mediate such effects will be defined. The mechanisms through which these signal operate will be characterized by analyses of transcription and translation. The role of specific HIV genes, particularly the regulatory genes tat and art/trs will be determined. Finally after the signals, factors and mechanisms involved in the response of one virus to the reciprocal virus have been delineated, the role of combined infection on expression regulated by these signals will be determined. These studies will reveal new insights into the molecular pathogenesis of AIDS.